Humans are highly social. Our brains have evolved to recognize and interpret the expression of faces and to produce and process language. Our behavior is modulated by our social interactions, and defects in social cognition manifest themselves in various disorders, including depression and autism. However, it has remained challenging to model these conditions in classic genetic systems such as rodents and flies because they only display basic social behaviors. Social insects such as ants, on the other hand, have evolved sophisticated societies and social behaviors, including nestmate recognition and complex communication via chemical cues. Their behavior is contingent on the social environment, giving rise to cooperation and division of labor. We study ants to understand the basic genetic and neurobiological mechanisms underlying these phenomena. Because most of the molecules that modulate social behavior, such as neuropeptides, biogenic amines, and epigenetic marks on DNA and histones are conserved from insects to mammals, many of the insights gained from ants will also be applicable to humans. Over the past five years we have developed tools for the clonal raider ant Ooceraea biroi, a species that combines complex social insect biology with unprecedented experimental control. We can now monitor social behavior using computer vision, measure, map, and pharmacologically manipulate candidate neuromodulators in the ant brain, and create stable gene knockout and transgenic lines using CRISPR technology. We will study the development, organization and activity of the ant antennal lobe, the part of the brain that processes the ants' sophisticated chemical language. We will also conduct a large unbiased screen to identify candidate neuromodulators that affect social behavior. We will then manipulate these candidates pharmacologically and genetically to describe their function in more detail. We will also genetically disrupt DNA methylation, a common epigenetic mark implicated in behavioral individuality and plasticity. Finally, we will study how communication and social behavior affect the performance of social groups in dynamic and challenging external environments. This work will elucidate how, on a molecular level, the brains of social partners interact. This work is innovative because it uses a novel and uniquely suited study species to take a complementary approach to important biological questions of biomedical relevance. It will produce additional tools and resources to further establish the clonal raider ant as a model system for behavioral genetics, and it will shed light on the molecular mechanisms underlying social behavior, which can then be studied further in other species including humans.